Evidence for two distinct P2‐purinoceptors subserving contraction of the rat anococcygeus smooth muscle

• Published in: British journal of pharmacology 1996-06, Vol.118 (3), p.537-542
• Main Authors: Najbar, Alicja T., Li, C.G., Rand, Michael J.
• Format: Article
• Language: English
• Subjects: 8SPT; Adenosine Diphosphate - pharmacology; Adenosine Triphosphate - pharmacology; Animals; anococcygeus muscle (rat); ATP/ADP analogues; Biological and medical sciences; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; P2X‐purinoceptors; P2Y‐purinoceptors; PPADS; Rats; Rats, Sprague-Dawley; reactive blue 2; Receptors, Purinergic - classification; Receptors, Purinergic - physiology; Striated muscle. Tendons; suramin; Suramin - pharmacology; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb15435.x

1 The effects of the P2‐purinoceptor agonists, adenosine 5′‐triphosphate (ATP), α, β‐methylene ATP (α, β‐MeATP), β, γ‐methylene ATP (β, γ‐MeATP), L‐β, γ‐methylene ATP (L‐β, γ‐MeATP), adenosine‐5′‐O‐(2‐thiodiphosphate) (ADPβS), and 2‐methylthio ATP (2‐MeSATP) were investigated on the isometric tension of the rat anococcygeus muscle. 2 Non‐cumulative additions of ATP (100–1500 μm), α, β‐MeATP (1–300 μm), β, γ‐MeATP (10–300 μm), L‐β, γ‐MeATP (3–100 μm) and ADPβS (1–100 μm) produced concentration‐dependent contractions, whereas 2‐MeSATP (1–100 μm) had no effect. The rank order of potency was α, β‐MeATP > L‐β, γ‐MeATP ≥ ADPβS > β, γ‐MeATP > > ATP > 2‐MeSATP. 3 Contractions to cumulative additions of ATP, α, β‐MeATP, β, γ‐MeATP and L‐β, γ‐MeATP were subject to desensitization whilst those to ADPβS were unaffected. 4 Contractions to ATP, α, β‐MeATP, β, γ‐MeATP and ADPβS were abolished by the non‐selective P2X/P2Y‐purinoceptor antagonist, suramin (100 μm). In contrast, contractions to ATP, α, β‐MeATP and β, γ‐MeATP were not affected by the non‐selective P1‐purinoceptor antagonist 8‐(p‐sulphophenyl)‐theophylline (8SPT, 30 μm). Blockade of P2X‐purinoceptors with the selective P2X‐purinoceptor antagonist pyridoxal‐phosphate‐6‐azophenyl‐2′, 4′‐disulphonic acid (PPADS, 10 μm) or desensitization with L‐β, γ‐MeATP (10 μm) abolished contractions to α, β‐MeATP, but enhanced those to ADPβS. The P2Y‐purinoceptor antagonist, reactive blue 2 (RB2, 100 μm) enhanced contractions to ATP and α, β‐MeATP but abolished those to ADPβS. 5 Simultaneous addition of α, β‐MeATP and ADPβS produced an additive contraction. 6 The findings suggest that in the rat anococcygeus, smooth muscle cells are endowed with two distinct P2‐purinoceptors which subserve contractions: a P2X‐purinoceptor activated by ATP and its analogues, and another type of P2‐purinoceptor activated by ADPβS.